The present invention relates to mixtures suitable for formulating hydrophobic and water-sensitive active agents, these mixtures when dried, processes for producing dosage forms from the mixtures in the wet or dry states and the dosage forms themselves.
Self-emulsifying drug delivery systems have been shown to be a method of increasing the bioavailability of poorly water soluble active agents, such as drugs, and are an alternative to traditional formulations of lipophilic active agents.
A self-emulsifying system is a mixture of oil and surfactant which forms a fine oil-in-water emulsion when introduced into an aqueous phase under conditions of gentle agitation. Such mixtures can be used as, for example, pharmaceutical oral drug delivery systems for lipophilic compounds by dissolving the drug in the oil phase. The system is expected to self-emulsify rapidly in the aqueous contents of the stomach, thereby presenting the drug in solution in small droplets of oil. The gentle agitation required for the emulsification is provided by the digestive motility of the stomach. Fine oil droplets should empty rapidly from the stomach and promote wide distribution of the drug throughout the gastrointestinal tract, thereby minimising irritation frequently encountered with extended contact between bulk drug substances and the gut wall. The self-emulsifying drug delivery systems also provide a large interfacial area across which the drug can diffuse into the gastrointestinal fluids. Since the drug is dissolved in the oil phase the dissolution step, which can be absorption rate limiting for poorly water soluble drugs, is eliminated.
Several combinations of oil and surfactant have been used to produce self-emulsifying systems. The ingredients most frequently used are medium chain triglyceride oils (vegetable oils) and nonionic surfactants, which are acceptable for oral ingestion. Factors affecting the efficiency of a self-emulsifying system are the HLB and concentration of the surfactant. The dosage forms which result from these systems are usually either liquids or hard or soft gelatin capsules.
A self-emulsifying system comprises i) microcrystalline cellulose and ii) an oily substance, surfactant, and water is useful for providing solid dosage forms of hydrophobic or water sensitive agents when dried or extruded and spheronised.